Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for elderly patients. Some drugs, although reasonable for use in younger adults, are so risky they should be considered inappropriate for the elderly. The Beers Criteria are most commonly used to identify such inappropriate drugs (see Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update)). The 2012 American Geriatrics Society updates to the Beers criteria further categorize potentially inappropriate drugs into 3 groups:

Inappropriate: Always to be avoided

Potentially inappropriate: To be avoided in certain diseases or syndromes

May cause pulmonary toxicity; safer alternatives available; lack of efficacy in patients with creatinine clearance < 60 mL/min due to inadequate drug concentration in the urine; do not use for long-term suppression or in patients with creatinine clearance < 60 mL/min

Analgesics

NSAIDs are used by > 30% of people aged 65 to 89, and half of all NSAID prescriptions are for people > 60. Several NSAIDs are available without prescription.

The elderly may be prone to adverse effects of these drugs, and adverse effects may be more severe because of the following:

NSAIDs are highly lipid-soluble, and because adipose tissue increases with age, distribution of the drugs is extensive.

Plasma protein is often decreased, resulting in higher levels of unbound drug and exaggerated pharmacologic effects.

Renal function is reduced in many of the elderly, resulting in decreased renal clearance and higher drug levels.

Serious adverse effects include peptic ulceration and upper GI bleeding; risk is increased when an NSAID is begun and when dose is increased. Risk of upper GI bleeding increases when NSAIDs are given with warfarin, aspirin, or other antiplatelet drugs (eg, clopidogrel). NSAIDs may increase risk of cardiovascular events and can cause fluid retention and, rarely, nephropathy.

NSAIDs can also increase BP; this effect may be unrecognized and lead to intensification of antihypertensive treatment (a prescribing cascade—see Drug Therapy in the Elderly:Drug-disease interactions). Thus, clinicians should keep this effect in mind when BP increases in elderly patients and ask them about their use of NSAIDs, particularly OTC NSAIDs.

Selective COX-2 (cyclooxygenase-2) inhibitors (coxibs) cause less GI irritation and platelet inhibition than other NSAIDs. Nonetheless, coxibs still have a risk of GI bleeding, especially for patients taking warfarin or aspirin (even at a low dose) and for those who have had GI events. Coxibs, as a class, appear to increase risk of cardiovascular events, but risk may vary by drug; they should be used cautiously. Coxibs have renal effects comparable to those of other NSAIDs.

Lower-risk alternatives (eg, acetaminophen) should be used when possible. If NSAIDs are used in the elderly, the lowest effective dose should be used, and continued need should be reviewed frequently. If NSAIDs are used long-term, serum creatinine and BP should be monitored closely, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use).

Anticoagulants

Age may increase sensitivity to the anticoagulant effect of warfarin. Careful dosing and routine monitoring can largely overcome the increased risk of bleeding in elderly patients taking warfarin. Also, because drug interactions with warfarin are common, closer monitoring is necessary when new drugs are added or old ones are stopped; computerized drug interaction programs should be consulted if patients take multiple drugs. Patients should also be monitored for warfarin interactions with food, alcohol, and OTC drugs and supplements. The newer anticoagulants (dabigatran, rivaroxaban, apixaban) may be easier to dose and have fewer drug-drug interactions and food-drug interactions than warfarin, but still increase the risk of bleeding in elderly patients, particularly those with impaired renal function.

Antidepressants

Tricyclic antidepressants are effective but should rarely be used in the elderly. SSRIs and mixed reuptake inhibitors, such as serotonin-norepinephrine reuptake inhibitors (SNRIs), are as effective as tricyclic antidepressants and cause less toxicity; however, there are some concerns about some of these drugs:

Paroxetine: This drug is more sedating than other SSRIs, has anticholinergic effects, and, like some other SSRIs, can inhibit hepatic cytochrome P-450 2D6 enzyme activity, possibly impairing the metabolism of several drugs, including tamoxifen, some antipsychotics, antiarrhythmics, and tricyclic antidepressants.

Citalopram: Doses in the elderly should be limited to a maximum of 20 mg/day because QT prolongation is a concern.

Venlafaxine: This drug may increase BP.

Mirtazapine: This drug can be sedating and may stimulate appetite/weight gain.

Antihyperglycemics

Doses of antihyperglycemics should be titrated carefully in patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase with age. As described in see Table: Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update), chlorpropamide is not recommended in elderly patients because of the increased risk of hypoglycemia and of hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Risk of hypoglycemia is also greater with glyburide than with other oral antihyperglycemics because its renal clearance is reduced in the elderly.

Metformin, a biguanide excreted by the kidneys, increases peripheral tissue sensitivity to
insulin
and can be effective given alone or with sulfonylureas. Risk of lactic acidosis, a rare but serious complication, increases with degree of renal impairment and with patient age. Heart failure is a contraindication.

Antihypertensives

In many elderly patients, lower starting doses of antihypertensives may be necessary to reduce risk of adverse effects; however, for most elderly patients with hypertension, achieving BP goals requires standard doses and multidrug therapy. Initial treatment of hypertension in the elderly typically involves a thiazide-type diuretic, ACE inhibitor, angiotensin II receptor blocker, or dihydropyridine Ca channel blocker, depending on comorbidities. β-blockers should be reserved for 2nd-line therapy. Short-acting dihydropyridines (eg, nifedipine) may increase mortality risk and should not be used. Sitting and standing BP can be monitored, particularly when multiple antihypertensives are used, to check for orthostatic hypotension, which may increase risk of falls and fractures.

Antiparkinsonian drugs

Levodopa clearance is reduced in elderly patients, who are also more susceptible to the drug’s adverse effects, particularly orthostatic hypotension and confusion. Therefore, elderly patients should be given a lower starting dose of levodopa and carefully monitored for adverse effects (see Levodopa). Patients who become confused while taking levodopa may also not tolerate dopamine agonists (eg, pramipexole, ropinirole). Because elderly patients with parkinsonism may be cognitively impaired, drugs with anticholinergic effects should be avoided.

Antipsychotics

Antipsychotics should be used only for psychosis. In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than placebo and can have severe adverse effects. In people with dementia, studies showed antipsychotics increased mortality and risk of stroke, leading the FDA to issue a black box warning on their use in such patients. Generally, dementia-related behavior problems (eg, wandering, yelling, uncooperativeness) do not respond to antipsychotics.

When an antipsychotic is used, the starting dose should be about one quarter the usual starting adult dose and should be increased gradually with frequent monitoring for response and adverse effects. Once the patient responds, the dose should be titrated down, if possible, to the lowest effective dose. The drug needs to be stopped if it is ineffective. Clinical trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited.

Antipsychotics can reduce paranoia but may worsen confusion (see also Conventional antipsychotics). Elderly patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. Sedation, orthostatic hypotension, anticholinergic effects, and akathisia (subjective motor restlessness) can occur in up to 20% of elderly patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6 to 9 mo after the drug is stopped.

Extrapyramidal dysfunction can develop even when 2nd-generation antipsychotics (eg, olanzapine, quetiapine, risperidone) are used, especially at higher doses. Risks and benefits of using an antipsychotic should be discussed with the patient or the person responsible for the patient's care. Antipsychotics should be considered for behavior problems only when nonpharmacologic options have failed and patients are a threat to themselves or others.

Anxiolytics and hypnotics

Treatable causes of insomnia should be sought and managed before using hypnotics (see also Hypnotics). Nonpharmacologic measures, such as cognitive-behavioral therapy, and sleep hygiene (eg, avoiding caffeinated beverages, limiting daytime napping, modifying bedtime) should be tried first. If they are ineffective, nonbenzodiazepine hypnotics (eg, zolpidem, eszopiclone, zaleplon) are options for short-term use. These drugs bind mainly to a benzodiazepine receptor subtype and disturb the sleep pattern less than benzodiazepines. They have a more rapid onset, fewer rebound effects, fewer next-day effects, and less potential for dependence. As described in see Table: Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update), short-, intermediate-, and long-acting benzodiazepines are associated with increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in the elderly and should be avoided for the treatment of insomnia. Benzodiazepines may be appropriate for treatment of anxiety or panic attacks in the elderly.

Duration of anxiolytic or hypnotic therapy should be limited if possible because tolerance and dependence may develop; withdrawal may lead to rebound anxiety or insomnia.

Antihistamines (eg, diphenhydramine, hydroxyzine) are not recommended as anxiolytics or hypnotics because they have anticholinergic effects, and tolerance to the sedative effects develops quickly.

Buspirone, a partial serotonin agonist, can be effective for general anxiety disorder; elderly patients tolerate doses up to 30 mg/day well. The slow onset of anxiolytic action (up to 2 to 3 wk) can be a disadvantage in urgent cases.

Digoxin

Digoxin, a cardiac glycoside, is used to increase the force of myocardial contractions and to treat supraventricular arrhythmias. However, it must be used with caution in elderly patients. In men with heart failure and a left ventricular ejection fraction of ≤ 45%, serum digoxin levels > 0.8 ng/mL are associated with increased mortality risk. Adverse effects are typically related to its narrow therapeutic index. One study found digoxin to be beneficial in women when serum levels were 0.5 to 0.9 ng/mL but possibly harmful when levels were ≥ 1.2 ng/mL. A number of factors increase the likelihood of digoxin toxicity in the elderly. Renal impairment, temporary dehydration, and NSAID use (all common among the elderly) can reduce renal clearance of digoxin. Furthermore, digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Also, if lean body mass is reduced, as may occur with aging, volume of distribution for digoxin is reduced. Therefore, starting doses should be low (0.125 mg/day) and adjusted according to response and serum digoxin levels (normal range 0.8 to 2.0 ng/mL). However, serum digoxin level does not always correlate with likelihood of toxicity.

Diuretics

Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension in many elderly patients and have less risk of hypokalemia and hyperglycemia than other diuretics (see also Diuretics). Thus, K supplements may be required less often.

K-sparing diuretics should be used with caution in the elderly; the K level must be carefully monitored, particularly when these diuretics are given with ACE inhibitors or angiotensin II receptor blockers or when the patient has impaired kidney function.

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